Department of Pathology, The Second Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, 050000, PR China; Laboratory of Pathology, Hebei Medical University, Shijiazhuang, Hebei Province, Shijiazhuang, Hebei, 050017, PR China.
Laboratory of Pathology, Hebei Medical University, Shijiazhuang, Hebei Province, Shijiazhuang, Hebei, 050017, PR China.
Eur J Surg Oncol. 2021 Feb;47(2):323-330. doi: 10.1016/j.ejso.2020.08.022. Epub 2020 Aug 26.
Mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) are rare tumors, mainly encountered in the gastroenteropancreatic tract. Based on the limited available data, MiNEN is usually a highly aggressive neoplasm combining a high-grade neuroendocrine and a non-neuroendocrine component, associated with a poor prognostic outlook. Deficient DNA mismatch repair (MMR) results in microsatellite instability, which is a useful screening marker for identifying patients with Lynch syndrome and a prognostic factor for chemotherapeutic interventions. Little information on MMR status in MiNEN is available in published studies. Therefore, the purpose of this study was to explore the status and putative role of MMR on MiNEN.
We investigated the MMR status in 44 cases and characterized their clinicopathological features and prognoses. Immunohistochemistry was performed for four mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2).
Mean age at diagnosis was 61 years, and 75% of the patients were male. Lymph node metastases were observed in 14 (35.9%) patients. The most common tumor localizations were gastric (28 patients, 63.6%). Lack of immunohistochemical expression of MMR proteins was shown in 38.6% of cases. The common deletion rates of one or more proteins were 29.4% (5/17) for MLH1/PMS2 and 23.5% (4/17) for MLH1. Correlation between clinicopathological parameters showed that MMR deficiency was significantly associated with early TNM stage and better prognoses in patients with MiNEN.
MiNENs showed frequent losses of MMR protein expression, which contributes to the knowledge of the pathological and clinical aspects of MiNEN tumors.
混合性神经内分泌-非神经内分泌肿瘤（MiNEN）是一种罕见的肿瘤，主要发生在胃肠胰神经内分泌肿瘤。基于有限的可用数据，MiNEN 通常是一种高度侵袭性的肿瘤，结合了高级别的神经内分泌和非神经内分泌成分，预后不良。错配修复（MMR）功能缺陷导致微卫星不稳定，这是识别林奇综合征患者的有用筛查标志物，也是化学治疗干预的预后因素。在已发表的研究中，关于 MiNEN 中 MMR 状态的信息很少。因此，本研究旨在探讨 MiNEN 中 MMR 的状态及其可能的作用。
我们研究了 44 例 MiNEN 的 MMR 状态，并对其临床病理特征和预后进行了分析。采用免疫组织化学方法检测四种错配修复蛋白（MLH1、MSH2、MSH6 和 PMS2）。
诊断时的平均年龄为 61 岁，75%的患者为男性。14 例（35.9%）患者发生淋巴结转移。最常见的肿瘤部位是胃（28 例，63.6%）。38.6%的病例显示 MMR 蛋白免疫组化表达缺失。一个或多个蛋白缺失的常见缺失率为 MLH1/PMS2 的 29.4%（5/17）和 MLH1 的 23.5%（4/17）。临床病理参数的相关性分析显示，MMR 缺陷与 MiNEN 患者的早期 TNM 分期和较好的预后显著相关。
MiNEN 中经常出现 MMR 蛋白表达缺失，这有助于了解 MiNEN 肿瘤的病理和临床方面。
